Medical devices for the detection, prevention and/or treatment of neurological disorders, and methods related thereto

ABSTRACT

Disclosed are devices and methods for detecting, preventing, and/or treating neurological disorders. These devices and methods utilize electrical stimulation, and comprise a unique concentric ring electrode component. The disclosed methods involve the positioning of multiple electrodes on the scalp of a mammal; monitoring the mammal&#39;s brain electrical patterns to identify the onset of a neurological event; identifying the location of the brain electrical patterns indicative of neurological event; and applying transcutaneous or transcranial electrical stimulation to the location of the neurological event to beneficially modify brain electrical patterns. The disclosed methods may be useful in the detection, prevention, and/or treatment of a variety of indications, such as epilepsy, Parkinson&#39;s Disease, Huntington&#39;s disease, Alzheimer&#39;s disease, depression, bipolar disorder, phobia, schizophrenia, multiple personality disorder, migraine or headache, concussion, attention deficit hyperactivity disorder, eating disorder, substance abuse, and anxiety. The disclosed methods may also be used in combination with other peripheral stimulation techniques.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.11/252,043, filed on Oct. 17, 2005, which is a continuation-in-part-ofU.S. patent application Ser. No. 10/967,891, filed on Oct. 18, 2004,which claims the benefit of U.S. Patent Application No. 60/511,914,filed on Oct. 16, 2003, each of which is incorporated by reference.

TECHNICAL FIELD

The present invention relates generally to medical devices, morespecifically, to medical devices for the detection, prevention, and/ortreatment of neurological disorders, and methods related thereto.

BACKGROUND

Epilepsy is one of several neurological disorders that can be severelydebilitating and/or dangerous. Epilepsy is characterized by theoccurrence of seizures, in particular episodic impairment, loss ofconsciousness, abnormal motor phenomena, psychic or sensorydisturbances. It is believed that as many as two to four millionAmericans may suffer from various forms of epilepsy. Research has foundthat its prevalence may be even greater worldwide, particularly in lesseconomically developed nations, suggesting that the worldwide figure forepilepsy sufferers may be in excess of one hundred million.

Traditional treatment modalities for epilepsy are moderatelyefficacious; however, they suffer from several severe drawbacks. Onesuch technique for controlling epilepsy involves the use of dopaminergicagonists or anticholinerigic agents. Managing epilepsy using thistechnique requires iterations in dosing adjustments to balance efficacyand side effects. A number of drugs are approved and available fortreating epilepsy, such as lorazopan, diazapan, sodium valproate,phenobarbital/primidone, ethosuximide, gabapentin, phenytoin, andcarbamazepine, among others. Unfortunately, these drugs typically haveserious side effects, especially toxicity. Further, it is extremelyimportant in most cases to maintain a precise therapeutic serum level toavoid breakthrough seizures (if the dosage is too low) or toxic effects(if the dosage is too high). The need for patient discipline is high,especially when a patient's drug regimen causes unpleasant side effectsthat the patient may wish to avoid. Moreover, while many epilepsypatients respond well to drug therapy alone, a significant number (atleast 20%-30%) do not. For those patients, surgery is presently thebest-established and most viable alternative course of treatment.

Commonly practiced surgical approaches for medically refractory epilepsyinclude surgical resection, such as hemispherectomy, corticectomy,lobectomy and partial lobectomy, and less-radical lesionectomy,transection, and stereotactic ablation. Surgery is not always completelysuccessful and generally has a risk of complications. Further, surgerycan result in damage to eloquent (i.e., functionally important) brainregions and the consequent long-term impairment of various cognitive andother neurological functions. Surgical treatments are contraindicated ina substantial number of patients for various reasons. Moreover, of thoseepilepsy patients who do undergo surgery, many are still notseizure-free after surgery.

Another traditional approach for controlling epilepsy is tissueablation. Tissue ablation is typically performed via stereotacticneurosurgical procedures, including pallidotomy, thalamotomy,subthalamotomy, and other lesioning procedures. These procedures areonly moderately efficatious.

Tissue ablation procedures not only pose inherent surgical risks, butthey also suffer from a number of fundamental limitations. One obviouslimitation is irreversibility of tissue removal or destruction. Thus,any excessive or inadvertent removal of tissue is final.

Electrical stimulation is an emerging method for treating epilepsy.However, currently approved and available electrical stimulation devicesapply continuous electrical stimulation to neural tissue surrounding ornear implanted electrodes, and do not perform any detection—simply theydo not respond to relevant neurological conditions. One example of anelectrical stimulation device is the NeuroCybernetic Prosthesis (NCP)from Cyberonics, Inc. The vagus nerve stimulator (VNS) of this device,for example, applies continuous electrical stimulation to the patient'svagus nerve. The VNS has been found to reduce seizures by about 50% inabout 50% of patients tested. Still, a much greater reduction in theincidence of seizures is necessary to provide substantial clinicalbenefit. Even though the VNS may change the electrical pattern of aseizure, and increasing the interictal time may allow eventual seizurecontrol, some studies in the literature suggest that quality of life isdependent upon the frequency of seizures and not necessarily theinterictal time. Hence, the ultimate goal of any antiepileptic therapyshould not simply be the facilitation of seizure reduction via changingthe seizure pattern or increasing interictal time, but should beactually stopping the seizures.

Electrical stimulation has also been utilized for the treatment of otherneurological disorders. For example, a commercially available product,the Activa deep brain stimulator, from Medtronic, Inc., is a pectorallyimplanted continuous deep brain stimulator intended primarily to treatParkinson's disease. This device supplies continuous electrical pulsesto a selected deep brain structure where an electrode has been implantedin a predetermined neurological region. Chronic high frequencyintracranial electrical stimulation is typically used for inhibitingcellular activity in an attempt to functionally mimic the effect oftissue lesioning. Acute electrical stimulation to neural tissue, andelectrical recording and impedance measurement from neural tissue aremethods commonly used in the identification of brain structures, such astarget localization, during neurosurgical operations for the treatmentof various neurological disorders.

Continuous stimulation of deep brain structures for the treatment ofepilepsy has not met with consistent success. To be effective interminating seizures, it is believed that stimulation should beperformed near the focus of the epileptogenic region. The focus is oftenin the neocortex, where continuous stimulation may cause significantneurological deficit with clinical symptoms, including loss of speech,sensory disorders, or involuntary motion. Alternatively, the focus ofgeneral seizures may move and would thus require insertion of electrodeswhere the focus moves. This, as well as other conventional treatmentmodalities, offer some benefit to patients with epilepsy; however, theirefficacy is often limited.

Accordingly, research has also been directed toward automatic responsiveepilepsy treatment based on a detection of imminent seizure. Neuropace,Inc. is presently developing and conducting clinical trials on animplantable responsive neurostimulator for epilepsy. Once again, thereare the risks involved with an implantable system. For episodes wherethe focus of the seizure moves, or where there is no clear focus, itwould be nearly impossible to place electrodes in every location where aseizure focus may be. Compromises must be made to minimize the number ofimplanted electrodes and maximize the efficacy. Another major concern isthat such a device cannot be implanted quick enough during an emergencyseizure that is pharmaco-resistant.

Trigeminal nerve stimulation is also a possible method fordesynchronizing seizure activity. Advanced Bionics, Inc. is currentlydeveloping an implantable device for the treatment of epilepsy thatinvolves the application of electrical stimulation to the trigemnialnerve. As with the vagus nerve, the trigeminal nerve does not project toall areas of the brain and cannot stop all seizures. Once again, thismethod will have the same concerns for implantable devices as with theabove-mentioned devices.

There has been only one anecdotal report in the literature aboutelectroconvulsive therapy (ECT) use in medically intractable seizures inhuman patients (Griesemer et al., Neurology; 1997 49(5):1389-92): onepatient experienced “change in a seizure pattern with cessation athigher intensity,” while the other experienced “decrease in spontaneousseizure frequency”. Surprisingly, no further studies to investigate thismethodology in an animal model or in a human clinical series are found.Electroconvulsive therapy (ECT) is performed using conventional EEGelectrodes that are not capable of focusing stimulation to a specificvolume of biological tissue. To perform ECT, strong muscle relaxants, aswell as sedation, are often used. Thus, the patient must be monitoredclosely.

It has been proposed that if one can apply electrical stimulation at ornear the foci, the origin of epileptiform activity, the efficacy ofseizure control will be increased. Finding the seizure foci usuallyinvolves very expensive and immobile imaging equipment, such as afunctional magnetic resonance (fMRI) system. Even with such an elaboratesystem, real-time analysis of the seizure activity still cannot beachieved. Another means for seizure foci localization is to drill holesinto the cranium, and insert electrodes to record and analyze theelectrical activity from the brain to determine the location of thefoci. The latter technique is extremely invasive, requires aneurosurgeon, and can lead to complications. Similar techniques areapplicable for the treatment of Parkinson's disease and otherneurological disorders. Another problem that neither of these techniquescan overcome is that the foci may move to various other locations. ThefMRI and other similar imaging systems, such as positron emissiontomography (PET), depend on blood flow changes, which can take manyseconds to minutes to occur and thus unable to capture images of fastchanging brain activity. A moving seizure focus is at best difficult tomap with electrodes inserted into the brain; it may take many electrodesand many holes in the cranium to track the moving foci.

The use of electroencephalogram (EEG) is another approach to epilepsytherapy. EEG is a method for recording brain electrical activitynon-invasively from the scalp surface. It can have very good temporalresolution, less than 1.0 ms per sample. EEG can also be a portablesystem and without being exceedingly expensive. However, EEG does haveits limitations, such as the difficulty of localizing, with the type ofelectrodes used, the sources within the brain due to the smoothingaffects of the skull and other body tissue.

There are various methods disclosing localizing mechanisms of biologicalelectrical activity. They all involve post processing of data acquiredfrom either disc or bipolar electrodes. Post processing involves eithercomparing simulated and measured potentials iteratively, or using a bankof software filters. The solution for source localization by thesemethods is not in real time, and the use of MRI/CT data is oftennecessary. In one example, magnetoencephalographic (MEG) is used tolocalize sources in the brain (see e.g., U.S. Pat. No. 6,697,660). Ithas high temporal resolution similar to EEG, however, it is very costly,not portable, and requires a special room to facilitate its use.

In another example, multiple spatial filters are used for thelocalization of electrical sources from EEG signals in the brain (seee.g., U.S. Pat. No. 5,263,488). This technique requires post processingand is limited in resolution due to the use of conventional EEGelectrodes.

In another example involving the localization of electrical sources inthe brain using EEG, (, MRI another method of imaging the head is usedfor determining the shape and thickness of the scalp, skull,cerebrospinal fluid, and brain (see e.g., U.S. Pat. No. 5,331,970). Oncethis information is acquired, then a computer model is developed and amathematical deblurring algorithm is applied to estimate the location ofthe sources on the cortical surface of the brain. This requires muchpost processing time to determine where the sources originate from andcannot be used in real-time.

A similar approach has been utilized for imaging electrical activity ofthe heart (see e.g., U.S. Pat. No. 6,856,830). This method involves therecording of ECG on the body surface, obtaining an MRI or CT image ofthe patient's torso, and entering both components into a heart-torsomodel. The ext step of this method involves post processing, whereby,the body surface potentials are calculated for sources in the heart andcompared to the measured body surface potentials. This procedure must berepeated iteratively until the two components are within a given preseterror range. Hence, this process cannot be performed in real-time.Further, there is no definite localization of the sources, and,distortion, due to global sources, is evident because the recording isperformed with ordinary ECG electrodes.

In another example, regular EEG recording techniques and/or MEG areused, and restrictions are placed on the location where the brainelectrical activity may be occurring (see e.g., U.S. patent application20030093004). This approach is limited by the fact that the location ofthe activity must be known prior to the performance of this technique inorder for this type of a system to resolve an inverse localization fromthe surface potentials. Further, this technique suffers from theblurring effects of the heads volume conductor.

In another example, electrical impedance plethysmography (EIP) issuggested for localizing electrical sources inside biological tissue(see e.g., U.S. patent application 20020038095). In EIP, impedancecharacterizations that are made over a period of time are used tolocalize changes in the body tissue. Electrical stimulation is injectedinto tissue and return signals are measured to determine the impedance.As sources below the surface interact with the injected signals, a mapof conductivities is developed, and a model is assembled from theseconductivities to iteratively localize sources in the tissue. This typeof device is still dependent on typical EEG electrodes, which acceptglobal signals distorting the localization process.

As the current approaches to therapy, which include systems that arepresently available and those that are under development, such as drugs,surgery and implantable systems, present a variety of complications,there is a need for a system and method to non-invasively detect, treat,and prevent neurological disorders, particularly epilepsy.

SUMMARY OF THE INVENTION

Electroconvulsive therapy is currently utilized for the treatment ofvarious disorders, such as depression. However, ECT, as well as othermethods of therapy, such as drug therapy and implantable systems, thatare currently being used for the treatment of various neurologicaldisorders present a variety of complications that limit their successfuluse and standardization of therapy.

In view of the above, there is a need for a minimally invasive medicaldevice that can detect, prevent and/or treat neurological disorders.Preferably, such a device will involve electrical stimulation, as thisapproach shows great potential to achieve the desired results. It isalso desirable to have detection, prevention, and/or treatment methodsthat are safe and effective, short in duration, and are non- orminimally invasive.

It is, therefore, an object of the present invention to provide such amedical device for the detection, prevention, and/or treatment ofneurological disorders that can yield the desired results in a safe andconsistent manner.

It is another object of the present invention to provide such a medicaldevice that is an electrical stimulator and feedback device, utilizing aunique electrode system for discriminating different electrical sourcesin a body's volume conductor by direct measurement of brain electricalactivity.

It is another object of the present invention to provide such a medicaldevice that is capable of enhancing localization of sources.

It is another object of the present invention to provide methods for thedetection, prevention, and/or treatment of neurological disorders.

It is yet another object of the present invention to provide a methodfor detecting, preventing, and/or treating seizures via the applicationof electrical stimulation.

It is a further object of the present invention to provide such methodsthat are safe and effective, with minimal invasion, and that have shorttreatment periods.

The present invention pertains to medical devices for the detection,prevention, and/or treatment of neurological disorders, based onelectrical stimulation. In one embodiment of the present invention, sucha device comprises a unique electrode system that can discriminatedifferent electrical sources in a body's volume conductor by directmeasurement of brain electrical activity. Preferably, the electrodecomprises at least one outer conductive element and one centralconductive element, with the outer conductive element(s) surrounding thecentral conductive element, and thereby forming a concentricconfiguration. This concentric ring electrode possesses very high globalsignal attenuation, which enhances the localization process. Theelectrode's conductive elements may be arranged in a concentricgeometric configuration of a ring, a square, a rectangle, an ellipse, ora polygon comprising any number of sides. The electrodes are fabricatedfrom a metal, a non-metallic conductive material, or a combinationthereof, wherein the metal or the non-metallic conductive material isbiocompatible, or comprises a conductive biocompatible coating

In one embodiment of the present invention, a bioelectric neuro devicecomprises a control module, one or more electrodes, and a power supply.The control module comprises a stimulation sub-system, a communicationsub-system, and a central processing unit (CPU). A clock may be attachedexternally to the CPU or it may be integrated therein. The electrodearbiter comprises a steering logic controller and one or more electronicswitches. The detection sub-system comprises one or more amplifiers, oneor more analog-to digital (A/D) converters, and a digital signalprocessor (DSP). The impedance sub-system comprises one or moreimpedance signal generators and an impedance controller. The stimulationsub-system comprises one or more stimulation signal generators, astimulation controller, and a high voltage supply.

In one embodiment of the present invention, wires from the electrodesare connected to electrode arbiter, and to detection and stimulationsub-systems. The wires carry signals, such as electroencephalogram (EEG)signals, from the electrodes to the electrode arbiter. The electrodes,attached to a portion of a patient, are stimulated by the stimulationsub-system via the electrode arbiter, whereby the electrodes becomeenergized. The electrodes are preferably attached to the scalp of apatient by placement on or under the scalp, or anywhere in between thescalp and the brain, or anywhere within the brain. The attachmentfacilitates the stimulation of the brain.

The present invention also pertains to methods for the detection,prevention, and/or treatment of neurological disorders.

In one embodiment, the method involves the positioning of at least onetwo-element electrode on a portion of a mammal; monitoring brainelectrical signal patterns of the mammal to identify the presence oronset of a neurological event; identifying the location of the brainelectrical patterns indicative of neurological event prior to theapplying of electrical stimulation; and; and applying electricalstimulation to beneficially modify the brain electrical patterns.

In one embodiment of the present invention, brain electrical signalsdirectly localize at least two specific volumes of tissue via at leastnine electrodes arranged in a specific configuration. In anotherembodiment, this direct localization is accomplished via a three-pole orgreater concentric electrode configuration.

The methods of present invention involve the transcutaneous,transcranial, or a combination, application of electrical stimulation.The electrical stimulation may be applied in the form of sustainedcurrent, pulsed current, specific pulse pattern, sustained voltage,pulsed voltage, or any combination thereof. The frequency of electricalstimulation suitable for use herein is a in the range of from about 0.1Hz to about 2500 Hz; the pulse width suitable for use herein is in therange of from about 10

sec to about 10 sec, and the duration of stimulation suitable for useherein is in the range of from about 15 sec to about 30 min.

The methods of the present invention involve the application of voltagein the range of from about 500 mV to about 2 kV, preferably from about30 volts to about 100 volts, and current amplitudes in the range of fromabout 0.01 mA to about 1000 mA, preferably from about 5.0 mA to about 50mA.

The methods of present invention also pertain to the use of thebioelectric neuro device to deliver electrical stimulation viaconcentric electrodes in combination with other peripheral stimulationtechniques, such as drugs.

The bioelectric neuro device of the present invention, and methodsrelated thereto may be minimally-invasive or, preferably, noninvasive.

The above summary of the present invention is not intended to describeeach illustrated embodiment or every implementation of the presentinvention. The figures and the detailed description which followparticularly exemplify these embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention may be more completely understood in consideration of thefollowing detailed description of various embodiments of the inventionin connection with the accompanying drawings, in which:

FIG. 1 schematically illustrates a control module of the bioelectricneuro device, according to an embodiment of the present invention;

FIG. 2 schematically illustrates the electrode arbiter of thebioelectric neuro device and its connectivity to other devicecomponents, according to an embodiment of the present invention;

FIG. 3 schematically illustrates the detection sub-system of thebioelectric neuro device and its connectivity to other devicecomponents, according to an embodiment of the present invention;

FIG. 4 schematically illustrates the configuration of tripolarconcentric electrodes for directly detecting two depth volumes,according to an embodiment of the present invention;

FIG. 5 schematically illustrates the configuration of a tripolarconcentric electrode to perform a pseudo-bipolar difference, accordingto an embodiment of the present invention;

FIG. 6 schematically illustrates the impedance sub-system of bioelectricneuro device and its connectivity to other device components, accordingto an embodiment of the present invention;

FIG. 7 schematically illustrates the stimulation sub-system ofbioelectric neuro device and its connectivity to other devicecomponents, according to an embodiment of the present invention;

FIG. 8 is a flow chart of the methods for detection, localization,and/or treatment of neurological disorders, according to an embodimentof the present invention;

FIG. 9 schematically illustrates a subject's head with tri-polarconcentric electrodes placed thereon, according to an embodiment of thepresent invention;

FIG. 10 graphically illustrates the configuration of nine electrodepositions arranged in an array for use in 5-point and 9-pointcalculations, according to an embodiment of the present invention;

FIG. 11 graphically illustrates the difference between the electricalsignals measured with the 5-point and the 9-point methods, with varyinglateral positions of the dipole, according to an embodiment of thepresent invention; and

FIG. 12 is a 2-dimensional representation of a ‘four concentric spheres’head model, according to an embodiment of the present invention,

While the invention is amenable to various modifications and alternativeforms, specifics thereof have been shown by way of example in thedrawings and will be described in detail. It should be understood,however, that the intention is not to limit the invention to theparticular embodiments described. On the contrary, the intention is tocover all modifications, equivalents, and alternatives falling withinthe spirit and scope of the invention as defined by the appended claims.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

The present invention pertains to medical devices for detecting,preventing, and/or treating neurological disorders, based on electricalstimulation. The present invention also pertains to methods fordetecting, preventing, and/or treating neurological disorders utilizingsuch devices.

1. Definitions

The term “bioelectric neuro device”, as used herein, refers to themedical device for the detection, prevention, and/or treatment ofneurological disorders via electrical stimulation.

The term “concentric”, as used herein, refers to electrode elementswherein larger elements surround the smaller elements. In a preferredembodiment, conductive elements configured as rings with consecutivelyincreasing radius surround a central conductive disc. In otherembodiments, the conductive elements that surround the central electrodeelement may be a square, rectangle, ellipse, or polygon comprising anynumber of sides.

The term “electrical source” or “electrical sources”, as used herein,refers generally to neurons or nerves that generate electrical signalsin the brain. However, man-made electrical sources, such as a deep brainstimulation, may also be contemplated here, as it may be desirable tolocalize such man-made sources.

The term “electrode”, as used herein, refers to an electric conductorthrough which an electric current enters or leaves an electrolytic cellor other medium.

The term “Laplacian” is derived from the second derivative of apotential after its French inventor Pierre Laplace (1749-1827), and asused herein, refers to the second spatial derivative of a sensedelectric potential measured by the concentric ring electrodes. TheLaplacian increases the spatial frequencies. When used to stimulate,these concentric ring electrodes similarly allow the electric field tobe focused more specifically into the tissue than typical electrodes.

The term “neurological disorder” or “neurological disorders”, as usedherein, refers to any disorder, disease, and/or syndrome due to orresulting from neurologic, psychiatric, psychologic, and/orcerebrovascular symptomology or origin. Neurological disorders include,but are not limited to, epilepsy or other another generalized or partialseizure disorder, Parkinson's Disease, Huntington's disease, Alzheimer'sdisease, Pick's disease, Parkinsonism, rigidity, hemiballism,choreoathetosis, dystonia, akinesia, bradykinesia, hyperkinesia,depression, bipolar disorder, anxiety, phobia, schizophrenia, multiplepersonality disorder, substance abuse, attention deficit hyperactivitydisorder, eating disorder, impaired control of aggression, or impairedcontrol of sexual behavior, headache, or chronic headache, migraine,concussion, post-concussive syndrome, stress-related disorder, or anycombination thereof.

The term “neurological event”, as used herein, refers to abnormal neuralactivity, such as a seizure, a migraine, or depression.

The term “stimulation”, as used herein, refers to an electrical signalor signals applied to the scalp, to or near brain tissue, or to skinsurface, such as on the face or neck.

The term “N”, as used herein, refers to an indefinite quantity orduplications of some item, e.g., from 1 to N.

The term “sensitivity”, used herein, refers to the ratio of the signaldetected by an electrode from an electrical source directly below thecenter of the electrode, to the signal detected by an electrode from anelectrode source not directly below the center of the electrode.

It is to be understood that the singular forms of “a”, “an”, and “the”,as used herein and in the appended claims, include plural referenceunless the context clearly dictates otherwise.

2. The Bioelectric Neuro Device

The medical device of the present invention, bioelectric neuro device100, an embodiment of which is illustrated in FIG. 1, comprises acontrol module 110, one or more electrodes 120, and a power supply 130.The bioelectric neuro device 100 may further comprise external equipmentfor viewing signals, device controls and wires. Depending on theapplication, the medical device of the present invention may differ inits function and/or configuration. For example, for the detection,prevention, and/or treatment of seizures, such as epileptic seizures,the device may be a seizure stimulator or fibrillator; for treatingdepression, the device may be a depression stimulator, and etc. Theseizure fibrillator's functions include detecting specific electricalactivity due to or resulting from a neurological disorder, such asepilepsy. The depression stimulator's functions include the detecting ofspecific electrical signals due to or resulting from depression.Regardless of its intended application, this device comprises a uniqueconcentric electrode design that can be used for direct depth detectionof electrical sources, source location on a body surface, andhigh-resolution electrical signal detection. Accordingly, thebioelectric neuro device has the capability to locate the source of theoriginating electrical activity. Further, this device is capable of morespecifically targeting areas and delivering more uniform stimulationthan is possible with conventional electrodes, to ameliorate theneurological disorder quickly. The bioelectric neuro device is alsocapable of comparing the states before and after the application ofstimulation to determine the necessity of further doses of stimulation.If it is determined that more stimulation is necessary, then the deviceis capable of applying further stimulation, and if it is determined thatno more stimulation is necessary, then the device continues to analyzethe electrical signals to determine if any future action is necessary.

The control module 110 of the bioelectric neuro device comprises anelectrode arbiter 111, a detection sub-system 112, an impedancesub-system 113, a memory sub-system 114, a stimulation sub-system 115, acommunication sub-system 116, and a central processing unit (CPU) 117. Aclock 117 a may be attached externally to the CPU 117 or it may beintegrated therein. The electrode arbiter 111, an embodiment of which isillustrated in FIG. 2, comprises a steering logic controller 111 a andone or more electronic switches 111 b. The detection sub-system 112, anembodiment of which is illustrated in FIG. 3, comprises one or moreamplifiers 112 a, one or more analog-to digital (A/D) converters 112 b,and a digital signal processor (DSP) 112 c. The impedance sub-system113, an embodiment of which is illustrated in FIG. 6, comprises one ormore impedance signal generators 113 a and an impedance controller 113b. The stimulation sub-system 115, an embodiment of which is illustratedin FIG. 7, comprises one or more stimulation signal generators 115 a, astimulation controller 115 b, and a high voltage supply 115 c.

The analog-to-digital converter 112 b, digital signal processor 112 c,digital memory 114, central processing unit, which may be amicrocomputer, 117, and amplifier 112 a components used in the device ofthe present invention may be any such component that is known in the artor is commercially available. The techniques to interconnect thesecomponents and to program them may be any such technique known in theart. Alternatively, the present device may utilize custom very largescale integration (VLSI) or hybrid circuits that comprise anycombination of these components or their functions.

In one embodiment of the present invention, wires from electrodes 120are connected to electrode arbiter 111, and to detection sub-system 112and stimulation sub-system 115, as shown in FIG. 1. The wires carrysignals, such as electroencephalogram (EEG) signals, from electrodes 120to electrode arbiter 111. The electrodes 120, attached to a patient'sscalp, are stimulated by the stimulation sub-system 115 via theelectrode arbiter 111, whereby the electrodes 120 inject currents intothe patient. The electrodes 120 may be attached to the scalp byplacement on or under the scalp, or anywhere in between the scalp andthe brain, or anywhere within the brain. The attachment facilitates thestimulation of the brain. In another embodiment, a separate set ofelectrodes 120 and associated wires are utilized with each sub-system.In such a configuration, the inclusion of electrode arbiter 111 may notbe necessary.

The bioelectric neuro device 100 of the present invention may beminimally-invasive or, preferably, noninvasive. This can be advantageousfor a variety of reasons. For example, no surgical procedure would needto be performed to implant the device before it can be used. Thus, thedevice can be applied to the person very quickly in an emergencysituation. Research shows that the sooner the action is taken to controlseizures, the better the outcome. Further, no surgical procedure wouldbe necessary to change the electrodes. The electrodes can be replacedeasily as needed. The existing electrodes can also be replaced withoutany surgical procedures if a new electrode design is determined to bemore efficacious. The location of the electrodes can also be changedwithout resorting to surgery. Only a reconfiguration of the electrodeattachment mechanism may be necessary to accomplish this task, and itcan be performed by a technician rather than a neurosurgical team.Moreover, batteries can be changed without the need for surgery. Thistask could be performed by anyone, such as a technician, rather than aneurosurgical team. These, and other such advantages, make the use ofthe bioelectric neuro device very cost-effective. One particularcost-effective aspect of this device is that one device can be used fortreating multiple people, whereas an implantable device can only be usedto treat one person. This can be particularly important from a medicalstandpoint, as it can be used in emergency situations to address theneeds of many rather than just one.

2.1 The Detection Sub-System

The detection sub-system 112 of a bioelectric neuro device 100, such asa seizure fibrillator, serves to detect neurological events. Thedetection sub-system 112 automatically detects neurological events. Inone embodiment of the present invention, the detection sub-system 112,as illustrated in FIG. 3, receives signals, e.g., EEG signals(referenced to the system ground), from the brain or other source, andprocesses them to identify a neurological event, such as an epilepticseizure or its precursor. The central processing unit (CPU) 117 andmemory sub-system 114 act to control and coordinate all functions of theseizure fibrillator. The CPU 117 transmits programming parameters andinstructions to the detection subsystem 112 via interconnections. Thedetection sub-system 112 transmits signals to the CPU 117 that identifythe detection of a neurological event. The detection sub-system 112 canalso transmit EEG and other related data into the memory sub-system 114for storage. Currently available memory technology is suitable for EEGstorage. For example, the EEG storage for a 42 electrode system using 16bits (two bytes) per sample at a sampling rate of 500 samples per second(5 times over sampling of frequencies up to 100 Hertz (Hz)) will require2,520,000 bytes per minute of data storage. Flash memory is commonlyavailable in 256 megabyte devices that would allow approximately 100minutes of data storage.

The detection sub-system 112 comprises one or more amplifiers 112 a, oneor more analog-to digital (A/D) converters 112 b, and a digital signalprocessor (DSP) 112 c. The amplifier 112 a may comprise further signalprocessing circuitry, such as a bandpass filter. The bandpass filter canoperate as a pre-filter to remove frequency components of a signal thatis extraneous to or could interfere with the higher-level detectionsub-system 112 components. Bandpass filters typically will limit low andhigh frequencies being transmitted. The bandpass filters that would benecessary for noninvasive application to the scalp surface may not usethe same frequency parameters as those used by invasive devices. On thescalp surface, the skin-to-electrode contact may cause more lowfrequency artefact content than from implanted electrodes. Movement ofthe subject may also cause more low frequency artefacts than would beseen using invasive electrodes. For an external noninvasive device, itmay be advantageous to set the high pass filter cutoff higher than foran invasive system. Typically, there is not much signal present in theelectroencephalographic activity beyond 40 Hz. If the low pass filter isset for 40 Hz, then a 60 Hz or 50 Hz notch filter may not be necessary.

These components are preferably modular and may comprise discretearchitecture, however, they may be integrated into a specializedintegrated circuit due to space, power or cost considerations. Thespecialized integrated circuit may be a single mixed type, or a dualtype containing one circuit for analog processing and one circuit forthe digital conversion and processing. The detection sub-system 112 mayexist as a stand-alone unit or it may be integrated with the electrodes,amplifiers 112 a, stimulation sub-system 115, or any other component ofthe stimulator device.

The components of detection sub-system 112 can be placed in or on thebody of a subject. For example, a detection sub-system 112 and othercomponents of the seizure fibrillator, can be placed under the skin of asubject, making the seizure fibrillator entirely self-contained withinthe body of a subject.

Typically, electrical activity occurring in the brain of a subject (asrecorded electroencephalographically) in the absence of any neurologicalevents is normal and usually of a constant signal with little change inmagnitude. During a neurological event, such as a seizure, theelectrical activity is synchronized and has additive effect, causinghigher or lower EEG than normal EEG.

In one embodiment, the detection sub-system 112 of a seizure fibrillatoruses a signal that has been filtered by a band-pass filter in order toidentify patterns of brain activity that characterize a neurologicalevent. Such a detection sub-system 112 may employ any of a number ofalgorithms to identify a seizure. Such algorithms can be adapted toidentify signal's components, which include, but are not limited to, themagnitude of the signal, the dominant frequency component of the signal,and time frequency analysis.

When a neurological event, such as a seizure, is detected by thedetection subsystem 112, the CPU 117 can command the stimulationsub-system 115 to transmit electrical signals to any one or more of theelectrodes 120 via the electrode arbiter 111 and wires. It isanticipated that, if appropriate electrical signals are transmitted tocertain locations in, on, or near the brain, the normal progression ofan epileptic seizure can be aborted. It may also be necessary for thestimulation subsystem 115 to temporarily disable the detection subsystem112 when stimulation is imminent, via the electrode arbiter 111 so thatthe stimulation signals are not inadvertently interpreted as aneurological event by the detection sub-system 112 or damage thedetection sub-system 112.

In another embodiment of the present invention, the detection sub-system112 sends a signal to the (CPU and then the) stimulation sub-system 115for a duration of time that a signal meets the requirements of a givenneurological event, and to not send signals to the stimulationsub-system 115 when the neurological event-related brain activityceases. That is, stimulatory signals are only sent when a neurologicalevent is present and stimulatory signals are not sent when the EEGsignals fall below the threshold value or do not meet a known pattern ofa neurological event. Sending signals to the stimulation sub-system 115only during periods in which neurological events are present may preventside effects. Further, doing so may minimize or eliminate any potentialdamage or harm to the tissue.

The detection sub-system 112 is capable of directly detecting differentdepth sources to facilitate the localization of sources; this feature isintegral to the unique electrode design. The different depth sources aredetected based on the analysis of the lead field of a concentric discand ring bipolar lead system. In such a system, the sensitivity dropsoff rapidly, 1/r⁴ for a dipole beyond the outer radius of the annulus(ring), and the sensitivity for locating radial dipoles reaches maximumat the gap between the disc and the ring. With a disc and two concentricrings around it, a tripolar electrode system can be viewed as twobipolar electrode systems: the disc and the smaller ring forming onebipolar system, and the disc and the larger ring forming a secondbipolar system. When an electrical source is located outside of the areaof the disc and smaller ring, but inside the area encompassed by thelarger ring, such as at the point “a” in FIG. 4, the signal detected bythe disc and smaller ring bipolar system is attenuated drastically by1/r⁴, while the signal for the disc and larger ring bipolar system isnot. The potential measured by the larger electrode would be more thanthat for the smaller electrode. If the source is within the radius ofthe smaller electrode, the potential measured by the smaller electrodewould be larger than the potential of the larger electrode. Therefore,each disc and ring bipolar system is spatially selective to sourceswithin the reach of their radii. If additional larger rings arecontinued to be included, the area over which the electrode system canlocalize electrical sources continues to be extended.

The source need not be on the plane of the electrodes. The same conceptis applicable for depth detection. In this way, specific depth rangescan be determined. Consider a source below the plane of the electrode,such as at the point “b” in FIG. 4. Its distance to the center of thedisc is outside the radius of the smaller ring bipolar electrode (IR),but inside the radius of a larger ring bipolar electrode (OR).Therefore, the signal detected by the disc and the smaller ring bipolarelectrode is attenuated drastically by 1/r⁴, while the signal for theouter, larger ring is not. The outer ring potential would be greaterthan that of the disc and middle ring difference potential.Alternatively, if the dipole is within the radius of the middle ring,the disc and middle ring difference potential would be greater than thatof the outer ring.

Direct localization of sources to specific volumes of tissue or to othermedium can be achieved with the unique concentric electrodeconfiguration of the present device, and may also be achieved withspecific configurations of conventional electrodes. This unique featureperforms significantly better with concentric electrodes than withconventional electrodes because concentric electrodes discriminateglobal sources more so than conventional electrodes. This globalattenuation feature limits noise originating from beyond the outerdistance of the concentric electrode. The hardware, i.e., the electrodesand circuitry, provides bipolar difference signals from the electrodes120 controlled by the detection sub-system 112 to the digital signalprocessor 112 c. These difference pairs are combinations of increasingelectrode size. First, the difference between the potentials of the discand the innermost ring is taken acquired in a bipolar arrangement[Disc-Ring(1)]; then the disc and the same ring are shorted together, asillustrated in FIG. 5, and the difference between the potentials of thenext larger ring and the shorted combination is taken measured as[½(Disc+Ring(1))−Ring(2)]. The average potential for the shortedelectrode elements is always used. This pseudo-bipolar difference methodis applicable for any number of concentric elements. The pseudo-bipolardifferences can be performed with electronic circuitry, or by takingdifferential inputs between the electrode elements and the referenceelectrode and combining the differential signals digitally with asoftware algorithm.

2.2 The Impedance Sub-System

The stimulation impedance sub-system 113 of the present invention isused to check the impedance between the skin and the electrode.Generally, signals are transmitted more effectively when the impedanceis low. In one embodiment of the present invention, the impedancesub-system 113, as illustrated in FIG. 6, is utilized to check andverify that skin-to-electrode contact is made and maintained. If theskin-to-electrode contact becomes too high, signals are degraded in bothdirections, i.e., to detection and from stimulation. The impedancesub-system 113 generates signals of known magnitude and frequencies, andinstructs the electrode arbiter 111 that specific electrode(s) 120 needto be tested for skin-to-electrode impedance. The impedance controller113 b determines which electrodes will be tested, and incorporates themin between stimulation waveforms or at the start of stimulation waveformsequences. The arbiter 111 routes the impedance testing signals to thespecific electrode(s) 120 and the return path of the signals to thedetection sub-system 112. The magnitude of the signal received is thencompared to the magnitude of the signal sent, and from Ohm's Law, thereal part of the skin-to-electrode impedance can be determined. At lowfrequencies suitable for use herein, such as from about 1 Hz to about500 Hz, preferably from about 100 Hz to about 200 Hz, theskin-to-electrode impedance will primarily be a real resistivecomponent. The stimulation sub-system 115 can also generate signals foruse in impedance detection, however, this may cause complications due tothe mismatch of stimulation signal generator specifications to theimpedance detection application. For example, the stimulation sub-system115 will typically apply stimulation in the milliamp range whereas theimpedance testing circuitry requires microamp range currents. Further,the stimulation sub-system 115 may produce less complex stimulationwaveforms than the impedance sub-system 113.

Implanted systems that are currently used may decline in efficacy overtime, due too an increase in electrode impedance, which results fromfibrotic encapsulation of the electrode. In one embodiment of thepresent invention, constant current stimulation is used.

As the impedance changes, the magnitude of the stimulation current willremain the same, as will the efficacy.

2.3 The Electrode Arbiter

The stimulation electrode arbiter 111 of the present invention is amultiplexing mechanism. It is used to make or break contacts betweenelectrode(s) and sub-systems, such as the stimulation sub-system. In oneembodiment of the present invention, the electrode arbiter 111, asillustrated in FIG. 2, allows the signals to be steered to and fromspecific electrodes 120. If separate electrode(s) are used for recordingand stimulation then an arbiter is not necessary. Each electrode 120 canbe connected to the three sub-systems—detection, impedance, andstimulation. The electrode arbiter 111's steering logic takes commandsfrom each of these sub-systems and determines which electrodes 120 toconnect to which sub-system. For example, when the stimulationsub-system 115 wants to apply stimulation to specific electrodes 120that have been determined to be overlying the area where a neurologicalevent is originating from, the stimulation sub-system 115 commands theelectrode arbiter 111 to connect it to those particular electrodes. Thearbiter 111 signals the detection sub-system 111 that those electrodes120 are about to be stimulated and are not connected to the detectionsub-system 112. Other electrodes 120 may still be connected to thedetection sub-system 112 to evaluate the effects of the stimulation onthe neurological event while the stimulation is ongoing. For quick andconsistent activation and deactivation, and to prevent switch bounce,electronic switches are utilized by the electrode arbiter 111. An arrayof connections mapping the various interconnections of the electrodes120 is possible with this electronic mechanism.

2.4 The Stimulation Sub-System

The stimulation sub-system 115 of the present invention may be initiatedmanually or automatically. Stimulation parameters may be inputted orprogrammed manually, or resident stimulation parameters may be usedautomatically.

In one embodiment of the present invention, FIG. 7 illustrates thestimulation sub-system 115, including its interconnections to othersub-systems. The stimulation sub-system 115 is used to stimulate thescalp, brain, or other biological tissue in response to a detectedneurological event. The preferred embodiment of the stimulationsub-system 115 comprises a stimulation controller and N stimulationsignal generators connected to the electrodes 120 through wires via theelectrode arbiter 111. The event detection signal from the CPU 117 isreceived by the stimulation controller, which first sends a signal viathe link to the electrode arbiter 111 to disconnect specificelectrode(s) 120 from the detection sub-system 112 and to prepare forpossible stimulation artefact during stimulation. The stimulationcontroller will then feed stimulation command signals to the stimulationsignal generator(s) for a specific pre-programmed time period. Thestimulation command signals may be simultaneous or may have a relativedelay with respect to each other. These delays can be downloaded by theinstruction and parameter download from the CPU 117. It may be desirablethat the delays be adjusted so that the stimulation signals from thestimulation signal generators reach the neurological event focus in thebrain at the same time and in-phase. Doing so may enhance performance ofthe stimulation subsystem 115 in turning off a neurological event.Alternately, experience may indicate that certain signals being out ofphase when they arrive at the neurological event focus may beparticularly efficacious in aborting a neurological event.

The stimulation command signals can be used to control the amplitude,waveform, frequency, phase and time duration of the stimulation signalgenerators' output signals, or any combinations of. Differentstimulation parameters can be applied to different electrode(s) 120, andthereby allowing interference patterns to be generated. The stimulationcontroller can also have several patterns of stimulation pre-programmedto run automatically when triggered by the CPU 117 after a neurologicalevent is detected, or the CPU 117 may be used to dictate the stimulationparameters. Such a preset stimulation pattern may include severalstimulation sequences with different frequencies, magnitudes and/orother combinations of stimulation parameters used for specific lengthsof time.

The typical stimulation signals generated by the stimulation signalgenerators 115 a are preferably biphasic (that is, with equal energypositive and negative of ground), with a typical frequency in the rangeof from about 10 Hz to about 250 Hz, although frequencies in the rangeof from about 0.1 Hz to about 2500 Hz may be effective. It is alsoenvisioned that pure DC voltages may be used, although they are lessdesirable. If frequencies above 30 Hz are used, the stimulation signalgenerators could be capacitively coupled to the electrodes 120 to blockthe DC voltages. The typical width of the biphasic pulse is preferablybetween about 50 microseconds and about 500 microseconds, although pulsewidths of about 10 microseconds to about 10 seconds may be effective fora particular patient. The pulse width of the positive and negativephases may be of different durations and/or magnitudes Typically,voltage is applied in the range of from about 30 volts to about 100volts, and current amplitudes in the range of from about 5.0milliamperes (mA) to about 50 mA. However, it may be necessary to usemagnitudes above 2000 V if the skin-to-electrode impedance is high,e.g., 40,000 ohms or greater. The current may also be effective and safebelow and above this typical range. Stimulation is applied for aduration of from about 15 seconds to as long as 30 minutes, preferably,from about 30 seconds to about 5 minutes.

Biphasic voltage (current) generation circuits are well known in the artof circuit design and need not be diagrammed here. Similarly, theprogramming code for enabling the stimulation controller to providedifferent command parameters to the stimulation signal generators iseasily accomplished using well known programming techniques.

If the waveform parameter modulated by the stimulation controllercontrol law is the stimulation voltage magnitude, the design would notbenefit from the independence of impedance variation as controlling thestimulation current would allow. Alternatively, regulation of thestimulus pulse width may be desired. In certain circuit implementations,the available resolution or bits for specifying the magnitude of pulsewidth may be greater than that for specifying the pulse voltage orcurrent. In such a case, if finer control of the magnitude of thestimulation is desired than is provided by the control of pulse currentor pulse voltage, then it may be desirable to modulate the pulse width.Selection between regulation of pulse voltage, pulse current, or pulsewidth as the regulated pulse amplitude parameter is determined by thestimulation controller, which may be set using communication via theoperator interface. In alternative embodiments, the modulation of pulsefrequency and the modulation of the number of pulses per burst areregulated. Other such characteristics may be regulated in addition to orinstead of the ones noted above.

In one embodiment, charge balanced biphasic waveforms are preferablyproduced. The net charge contained in a given pulse is determined by thetime integral of the stimulus current over the duration of the pulse. Ina biphasic configuration, a pair of pulses of opposite polarity isgenerated, and the pulse current amplitude and pulse width are chosensuch that the charge amplitude is equal in magnitude and opposite inpolarity. In some cases, it is desirable for the pulses comprising thebiphasic pulse pair to have different amplitudes; in this case, thepulse widths are selected to insure equal and opposite charges such thatthe pulse pair introduces zero net charge to the biological tissue.

Although the waveform parameters of the pulse pairs are calculated todeliver a zero net charge, in practice, noise and precision limitationsand nonlinearities in the digital to analog conversion and amplificationstages may result in slight imbalances in the pulse pair charges. Overtime, this can result in the delivery of a substantial accumulated netcharge to the biological tissue. To eliminate this potential for netcharge delivery to neural tissue, a direct current (DC) blockingcapacitor is employed. This technique is well known in the art. In onepreferred embodiment, a DC blocking capacitor is included in series withthe stimulator output path.

It is also expected that by applying the stimulation from multiple setsof electrodes there will be a summation of intensity at the locationwhere the stimulation is focused, a superposition affect. This will bebeneficial because it will require less stimulation intensity from eachset of electrodes, lowering the risk of tissue damage. Lowering theintensity will also lessen the chance of stimulating non-seizureaffected areas of the brain.

The feedback control signal for the detector/stimulator combination ispreferably but not limited to, an EEG signal, and/or EMG and EOG. Whilea neurological event is being detected, stimulation is applied. This isbasically a proportional control. If stability and performancerequirements dictate, other components, such as an integrator and/or adifferentiator, may be added to the control law to produce aproportional-integral-differential (PID) controller.

A power supply provides power to each component of the device. Such apower supply typically utilizes a primary (rechargeable) storage batterywith an associated DC to DC converter to obtain the necessary voltagesas required by the bioelectric neuro device.

2.5 The Communication Sub-System

The communication sub-system 116 of the present invention may be used toenable external communication to and from the bioelectric neuro device.In one embodiment of the present invention, the bioelectric neuro devicecomprises radio telemetry-based components that can be employed towirelessly transmit or download stored EEG signals, detectionparameters, or other parameters, to a computer, a data storage, oranalysis component or device. A new detection algorithm can also bedownloaded into the detection sub-system 112 via radio telemetry or anyother method.

In one embodiment, the data stored in the memory of the device isretrieved by a physician via a wireless communication link while thedata communication sub-system is connected to the central processingsystem 117. Alternatively, an external data interface can be directlyconnected with an RS-232 type serial connection or USB connection to anexternal physician's or operator's workstation. Alternately, the serialconnection may be via modem(s) and phone line from the patient's home,emergency vehicle, or a remote area to the physician's workstation. Thesoftware in the computer component of the physician's workstation allowsthe physician to obtain a read-out of the history of events detected,including EEG information before, during and after the neurologicalevent, as well as specific information relating to the detection of theneurological event, such as spiking frequency of the patient's EEG. Theworkstation also allows the physician or operator to specify or alterthe programmable parameters of the bioelectric neuro device. RFtransceiver circuitry and antennas for this purpose are used widely inmedical device data communication.

2.6 The Real-Time Clock Sub-System

A real time clock 117 a, which is attached externally to the CPU 117 orintegrated therein, is used for timing and synchronizing variousportions of the bioelectric neuro device, and for enabling the device toprovide the exact date and time corresponding to each neurological eventdetected by the device and recorded in memory. In one embodiment of thepresent invention, the CPU 117 sends data to the real-time clock 117 ain order to set the correct date and time in the clock 117 a.

2.7 The Concentric Electrode

The electrode 120 for use herein may be a surface electrode or animplantable electrode, with each type possibly having different physicaland material properties. The electrode 120 may be soft, pliable, andflexible enough to conform to the tissue it is contacting, it may bestiff, or it may be any variation in between. The conductive electrode120 may be fabricated from a variety of metals, such as gold, platinum,or iridium, nonmetals, such as conductive polymers or any combinationthereof that are biocompatible or having conductive biocompatiblecoatings. Each electrode 120 has a multi-polar configuration, andcomprises at least two conductive elements, although electrodeembodiments having three elements, tripolar, are primarily disclosedherein. One or more conductive elements surround a central conductiveelement, such as a disc, in a concentric configuration. The width of theconductive elements can vary such that an increase in width inverselyaffects spatial resolution. The conductive elements are configured suchthat a gap is formed therebetween. The gap between the electrodes ispreferably equal to the width of the conductive elements to ensure bestapproximation to the Laplacian. This gap may be adjusted to performspecific spatial filters, such as exponential filtering.

The many unique features of the bioelectric neuro device provides themedical device of the present invention with a variety of advantages. Inone embodiment, the bioelectric neuro device performs automateddetermination of the treatment dosage. This dosage includes theselection of the number of electrodes for stimulation, electrodepolarities, electrode configurations, stimulation frequencies,stimulating parameter waveforms, temporal profile of stimulationmagnitude, stimulation duty cycles, baseline stimulation magnitude,intermittent stimulation magnitude and timing, and other stimulationparameters. This automation capability provides an added advantage tothe bioelectric neuro device.

In one embodiment, the bioelectric neuro device provides signalprocessed sensory feedback signals to clinicians so as to assist theirmanual selection of optimum treatment magnitude and pattern. Sensoryfeedback signals provided to the clinician, via a clinician-patientinterface include, but are not limited to, location of seizure foci,interictal rates, tremor estimates, EEG signals, and other signals.

In one embodiment, the unique concentric electrodes of the bioelectricneuro device allow for enhancement of the acquisition of localelectrical signals, while sharply attenuating electrical signals frommore distant sources.

In one embodiment, the unique concentric electrodes of the bioelectricneuro device directly measure the depth and surface location ofelectrical activity without other imaging modalities, such as CT, PET,MRI. This in particular is useful for localizing abnormal neurologicalsources. Once the sources have been localized, then they can be targetedwith focused electrical stimulation.

In one embodiment, the concentric electrodes of the bioelectric neurodevice are used for stimulation. The same benefit of enhancing detectionof local electrical signals holds true when applying electricalstimulation, due to reciprocity. The stimulation can be focused tospecific volumes of biological tissue (or other medium) with the use ofthe concentric electrodes.

In one embodiment, the bioelectric neuro device is used for applyingelectrical stimulation concurrently from multiple concentric electrodesthat originate from different sites, and are directed at a particularlocation; the stimulation intensities will sum when their paths cross.Therefore, the stimulation intensity from individual electrodes can bereduced, and thereby increasing the safety factor.

Although the present disclosure describes medical devices havingconcentric ring electrodes, other electrode configurations, such asrectangles, ellipses, or polygons such as triangles or pentagons mayalso be utilized. However, the approximation to the Laplacian for suchelectrodes will be deteriorated. In some possible circumstances, it maybe advantageous to utilize noncircular electrode configurations toperform spatial filtering of signals prior to the electronicacquisition, such as exponential or elliptical filtering.

3. Methods for the Detection, Prevention, and/or Treatment ofNeurological Disorders

The methods for detection, prevention, and/or treatment of neurologicaldisorders using the bioelectric neuro device of the present inventionare described hereinbelow. The flow chart in FIG. 8 illustrates thedecision path used to effectuate these methods. The basic means ofoperation involves the system being placed on the subject, asillustrated in FIG. 9.

In one embodiment, a neurological event is detected by the physician andverified by the detection sub-system 112.

In another embodiment, the detection sub-system 112 automaticallydetects the neurological event. Once the neurological event has beendetected, the location of the origin of the neurological event isdetermined for events that have a specific origin, such as in epilepsy.Thereafter, electrical or other stimulation or a combination is appliedto treat the neurological event. The signals are re-accessed todetermine whether the neurological event has been controlled, if notthen stimulation is re-applied. Each neurological event will havespecific characteristics that will allow the detection sub-system todiscriminate different neurological disorders, diseases, or syndromesusing the same basic hardware but different detection algorithms anddata bases for pattern matching. To prevent neurological events, thestimulation can be applied prior to a neurological event that has beenpredicted to occur or at intermittent intervals as needed. The detailsare described below.

3.1 Neurological Event Detection

Past work on the detection and responsive treatment of seizures viaelectrical stimulation has dealt with the analysis of EEG andelectrocorticogram (ECoG) waveforms. In general, EEG signals representaggregate neuronal activity potentials detectable via electrodes appliedto a patient's scalp. ECoG signals, deep-brain counterparts to EEGsignals, are detectable via electrodes implanted on or under the duramater, and usually within a patient's brain. Unless the context clearlyand expressly indicates otherwise, the term “EEG” shall be usedgenerically herein to refer to both EEG and ECoG signals.

To improve the efficiency of the seizure control, the focus of theseizure activity is located prior to applying electrical stimulation. Aunique method and device of the present invention can directly determinethe depth, Z, and the X, Y locations of the electrical sources. Thislocalization is utilized in locating the electrical activity origin ofthe neurological disorder. The methods for using EEG signals forlocalization are quite unique. The bioelectric neuro device preferablyuses the pseudo-bipolar method to detect the depth of electric sourcesas described in the “detection sub-system”. Or, concentric electrodesare configured in a form of 5-point or 9-point method for deeper depthdetection. Conventional electrodes can also be arranged to approximateconcentric electrodes for the purpose of depth detection. Consideringthe configuration shown in FIG. 10, where v₀, v₁ through v₈ arepotentials measured by conventional disc electrodes placed at thoselocations respectively, the potential difference P₅ of the 5-pointmethod is given as:

$\begin{matrix}{P_{5} = {v_{0} - {\frac{1}{4}\left( {v_{1} + v_{2} + v_{3} + v_{4}} \right)}}} & (1)\end{matrix}$

A variation of the 5-point method, the 9-point method is used forcalculating the potential difference P₉ as:

$\begin{matrix}{P_{9} = {{\frac{1}{2}\left( {v_{0} + {\frac{1}{4}\left( {v_{1} + v_{2} + v_{3} + v_{4}} \right)}} \right)} - {\frac{1}{4}\left( {v_{5} + v_{6} + v_{7} + v_{8}} \right)}}} & (2)\end{matrix}$

The 9-point method has an attenuating effect similar to the 5-pointmethod. However, because the nine electrodes cover a larger surface thanthe five electrodes, the attenuating effect tends to start at furtherdistances from the source. This rather sluggish effect of the 9-pointmethod can be seen from the comparison illustrated in FIG. 11. Theslopes of the potentials from the 5-point and 9-point methods aredifferent, as the slope of the 5-point method is steeper than the slopeof the 9-point method. This difference in the response of the 5-pointmethod and 9-point method for varying source location can be used toquantize the depth of a dipole source. As disc electrodes are not aseffective at global signal rejection, concentric electrodes are used inthe device and methods of the present invention to directly determinethe depth of an electrical source.

Upon the determination of the depth of the electrical source with themultiple sized concentric electrodes, the X, Y location is defined.Solving equation (8) results in the location of P (X,Y) of a dipole.Here, it is assumed that the depth dz is known or measured through somemethod, such as the pseudo-bipolar difference method. The potentialsmeasured by the electrodes are then used for localization of theelectrical source in a multi-conductivity medium. It is expected thatgreater potentials will be observed on electrodes that are closer to thesource than those farther.

The Laplacian potential at the center of the electrode can beapproximated in a bipolar concentric ring electrode by equation (4):

$\begin{matrix}{{{LP}\; 1} \cong {\frac{4}{\left( {2\; r_{o}} \right)^{2}}\left\{ {V_{{oring}\; 1} - V_{{disc}\; 1}} \right\}}} & (4)\end{matrix}$

where, V_(disc1) is the potential on the disc electrode, V_(oring1) isthe potential on the outer ring, r_(o) is the radius of outer ring, andLP1 is the calculated Laplacian potential using the bipolar electrode.The tri-polar concentric Laplacian potential has previously been provenby the inventor to be approximated by equation (5):

$\begin{matrix}{{{LPN}\; 1} \cong {\frac{1}{3\; r_{o}^{2}}\left\{ {{16\left( {V_{{oring}\; 1} - V_{{disc}\; 1}} \right)} - \left( {V_{{mring}\; 1} - V_{{disc}\; 1}} \right)} \right\}}} & (5)\end{matrix}$

where, V_(disc1) is the potential on the disc electrode, V_(mring1) isthe potential on middle ring, V_(oring1) is the potential on outer ring,is the radius f_(o) f outer ring, and LPN1 is the calculated Laplacianpotential for the tri-polar electrode.

The potential on the electrodes is given by equation (6). The distanceof the dipole from the center of the sphere is taken as R. Referring toFIG. 12, R≦R₄, and the line joining the dipole at position P and theelectrode disc P₁ cuts the inner sphere (with radius R₄) at position P₄(in the direction of PP₁) and similarly intersects the other two spheresat positions P₃ and P₂, respectively. Then, the potential on the surfaceelectrode due to a dipole at position P is given as:

$\begin{matrix}{V_{{PE}\; 1} = {\frac{q}{4\; \pi}\left\lbrack {\frac{{dz}_{4}}{{\sigma_{4}\left( {PP}_{4} \right)}^{3}} + \frac{{dz}_{3}}{{\sigma_{3}\left( {P_{4}P_{3}} \right)}^{3}} + \frac{{dz}_{2}}{{\sigma_{2}\left( {P_{3}P_{2}} \right)}^{3}} + \frac{{dz}_{1}}{{\sigma_{1}\left( {P_{2}P_{1}} \right)}^{3}}} \right\rbrack}} & (6)\end{matrix}$

where, V_(PEI) is the potential on the electrode, and PP₄ is thedistance between positions P and P₄. Similarly, P₄P₃, P₃P₂, P₂E₁ are thedistances between each of those points, and dz₄ is the differencebetween the z-coordinate of P and P₄. Similarly, dz₃ is between P₄ andP₃, dz₂ is between P₃ and P₂, and dz₁ is between P₂ and P₁

The Laplacian potential for bipolar and tripolar electrodeconfigurations is calculated by equations (4) and (5) and is representedin equation (8) as exp, and the analytical Laplacian of the surfacepotentials is calculated using equation (7) and is represented inequation (8) as cal.:

$\begin{matrix}{{LPN}_{1}^{cal} = {\frac{\partial^{2}V_{{PE}\; 1}}{\partial X_{d}^{2}} + \frac{\partial^{2}V_{{PE}\; 1}}{\partial Y_{d}^{2}}}} & (7)\end{matrix}$

where, LPN₁ ^(cal) is the calculated Laplacian Potential and V_(PEI) isthe potential on the disc given by equation (6). The localization isperformed using equation (8)

$\begin{matrix}{{\begin{pmatrix}X_{d} \\Y_{d}\end{pmatrix}^{({I + 1})} = {\begin{pmatrix}X_{d} \\Y_{d}\end{pmatrix}^{(I)} + {\left( {A^{T}A} \right)^{- 1}{A^{T}\left( {{\overset{\_}{LPN}}^{\exp} - {\overset{\_}{LPN}}^{cal}} \right)}}}}{{where},\begin{pmatrix}X_{d} \\Y_{d}\end{pmatrix}^{({I + 1})}}} & (8)\end{matrix}$

is the localized position of the dipole due to iteration (I+1), andmatrix A^(T) is the transpose of matrix A given as:

$\begin{matrix}{A^{T} = \begin{bmatrix}\frac{\partial{LPN}_{1}^{cal}}{\partial X_{d}} & \frac{\partial{LPN}_{2}^{cal}}{\partial X_{d}} & \frac{\partial{LPN}_{3}^{cal}}{\partial X_{d}} \\\frac{\partial{LPN}_{1}^{cal}}{\partial Y_{d}} & \frac{\partial{LPN}_{2}^{cal}}{\partial Y_{d}} & \frac{\partial{LPN}_{3}^{cal}}{\partial Y_{d}}\end{bmatrix}} & (9)\end{matrix}$

Of course, the above description is for calculated potentials in acomputer model. In a real system, the potentials on the electrodes areautomatically measured and used to directly solve the X,Y position withequation 8 and depth Z using the pseudo-bipolar method or some othermethod.

Another method for localizing the depth of an electrical source involvesa transfer function. It is generally known that the potential measuredat the surface, or away from the source, depends on the electricalsource dipole moment and the position of the electrical source in thevolume conductor. It is also known that the potentials measured, whetheron the surface or within a volume conductor, also depend on theelectrode's dimensions and shape.

There are many expressions that relate the surface potential to theelectrode dimensions and shapes or to the position in a plane parallelto the surface. However, here is no record of any analytical expressionthat takes into account the 3D position of an electrical source and theshape and dimension of the electrode system at once.

As applicable to the present invention, an analytical expression thatgives the potential measured by a disc electrode on the surface of avolume conductor due to a radial dipole inside a volume conductor isdefined as:

$\begin{matrix}{{\underset{Disc}{\int\int}\varphi_{R}} = {\frac{q}{4\; \pi^{2}r_{d}^{2}\sigma}\sqrt{\frac{r_{d}}{x_{p}}}{\quad{\begin{bmatrix}{{{Log}\left\lbrack \frac{{{- \sqrt{\frac{r_{d}}{x_{p}}}}\left( {x_{p} + y_{p}} \right)} + \sqrt{z_{p}^{2} - {rx}_{p} + x_{p}^{2} + \left( {r_{d} + y_{p}} \right)^{2}}}{{\sqrt{\frac{r_{d}}{x_{p}}}\left( {x_{p} - y_{p}} \right)} + \sqrt{z_{p}^{2} - {rx}_{p} + x_{p}^{2} + \left( {r_{d} - y_{p}} \right)^{2}}} \right\rbrack} +} \\{{iLog}\left\lbrack \frac{{{- i}\sqrt{\frac{r_{d}}{x_{p}}}\left( {x_{p} + y_{p}} \right)} + \sqrt{z_{p}^{2} + {rx}_{p} + x_{p}^{2} + \left( {r_{d} - y_{p}} \right)^{2}}}{{i\sqrt{\frac{r_{d}}{x_{p}}}\left( {x_{p} - y_{p}} \right)} + \sqrt{z_{p}^{2} + {rx}_{p} + x_{p}^{2} + \left( {r_{d} + y_{p}} \right)^{2}}} \right\rbrack}\end{bmatrix},{{x_{p} \neq {0\underset{Disc}{\int\int}\varphi_{R}}} = 0},{x_{p} = 0}}}}} & (10)\end{matrix}$

wherein, Φ is the potential measured at the surface, q is the charge ofthe dipole, (xp, yp, d) is the location of the dipole, σ is theconductivity of the material of volume conductor, and r is the radius ofthe disc.

This equation can be extended easily to determine the potential asmeasured due to rings concentric to this disc electrode. Therefore, thisexpression for the disc and multiple rings combined together gives thedepth perception, which is not possible by any other expressiondisclosed in the prior art.

As illustrated in FIG. 1 and FIG. 3, the detection sub-system has thebuilt-in capability and the ability to receive new detection algorithmsfor detection of neurological disorders. There are many types ofalgorithms generally disclosed for this purpose, and they can beutilized by this detection sub-system. The use of the concentricelectrodes with these detection algorithms should improve the algorithmefficiency, as the concentric electrodes have been shown to possesssignificant signal detection advancements over conventional electrodes.

A. Detection and Localization of Epileptic Activity

The first task of controlling an epileptic seizure is to know that it isoccurring. This can be determined by some means external to, or by thebioelectric neuro device, e.g., seizure fibrillator. Preferably, theseizure is identified as it occurs; but it is more preferable that theseizure is identified before it occurs. An algorithm can be employed toidentify pre-seizure activity. A hallmark of seizure-related brainactivity is the appearance of signals comprising large changes involtage values (i.e., spikes) in an EEG signal profile. Such spikes canarise by hyper-synchronization of brain activity and will quantitativelyexceed those voltage measurements associated with normal, non-seizurerelated, brain activity. Therefore, in general the presence of a seizurecan be identified by the presence of voltage spikes in an EEG signalprofile.

In one embodiment, a seizure detection sub-system of a seizurefibrillator detects the presence of a seizure by comparing incoming EEGsignals, which can be bandpass filtered to predetermined levels, with apredetermined threshold value or other pattern of brain activityassociated with an epileptic seizure or condition. The seizure detectionsub-system can employ standard circuitry and/or software to analyzeincoming data and perform comparisons between incoming data and theseizure detection algorithm.

A seizure detection algorithm can be adapted to “learn” specificcharacteristics of a subject's brain activity before, during, and evenafter the occurrence of an epileptic seizure. In this way, a seizuredetection algorithm can store one or more parameters, which aremonitored during an epileptic seizure of a subject. At a later time,after the seizure has been controlled, the seizure detection algorithmincorporates the data into the algorithm itself. Preferably, when alater seizure occurs, or is predicted to occur, the seizure detectionalgorithm recognizes the onset of the seizure, based on measured data,and counteracts the seizure at an early point in time. It is preferablethat a seizure detection algorithm be adapted to evolve over time insuch a fashion as to make the algorithm more effective at recognizingand preventing and/or controlling a seizure.

An operator can preset the seizure detection algorithm. This seizuredetection algorithm can be set manually either before or after the finalset up of the seizure fibrillator, via the operator's communicationinterface. Appropriate seizure detection algorithms will be apparent tothose skilled in the art upon consideration of the present disclosure.The proper seizure detection algorithm can be altered and adapted asnecessary, which can facilitate the detection sub-system improving overtime, and thereby continually increasing the efficiency of seizuredetection, which in turn may lead to a more efficient application ofelectrical stimulation. Over a longer period of time, this may result ina lowered seizure frequency and improved quality of life for theafflicted person(s). It is preferable that a seizure detection algorithmbe adapted to evolve over time in such a fashion as to make thealgorithm more effective at recognizing and preventing and/orameliorating a seizure.

B. Detection and Localization of Pain

It should be understood that multiple methods may be used to determinethe site(s) where the electrode(s) may need to be located in order tocontrol the pain, such as headaches. Because the location of headachepain will vary from patient to patient, the precise location (orlocations) of electrode(s) placement should be determined on anindividual basis. Stimulation of the electrode(s) is preferablyperformed at the time of the diagnosis to identify the optimalstimulation site or sites for maximum pain relief. The bioelectric neurodevice can be controlled by the operator, who may be a physician,therapist, or even by the patient, on a self-administered dosage asnecessary.

The hardware and methods described previously for detection andlocalization of epileptic activity are generally similar to those usedfor detection and localization of pain. There are certainelectroencephalographic patterns evident for different types of pain.Empirical databases can be assembled for persons suffering from saidmanifestations, and the data can be used comparatively to determine if apatient's electroencephalogram matches any of the manifestations in thedatabase. If a match is found, an appropriate therapy can be provided toalleviate the pain. Stimulation at particular areas may be used to helplocalize and diagnose specific types of pain originating from specificlocations.

The methods of the present invention can be used to treat pain that maybe caused by a variety of conditions, including, but not limited to,migraine headaches, which including migraine headaches with aura,migraine headaches without aura, menstrual migraines, migraine variants,atypical migraines, complicated migraines, hemiplegic migraines,transformed migraines, and chronic daily migraines; episodic tensionheadaches; chronic tension headaches; analgesic rebound headaches;episodic cluster headaches; chronic cluster headaches; cluster variants;chronic paroxysmal hemicrania; hemicrania continua; post-traumaticheadache; post-lumbar puncture headache; low cerebro-spinal fluidpressure headache; chronic migraneous neuralgia, cervical headache;post-traumatic neck pain; post-herpetic neuralgia involving the head orface; pain from spine fracture secondary to osteoporosis; arthritis painin the spine, headache related to cerebrovascular disease and stroke;headache due to vascular disorder (such as atriovenous malformation);arthritis pain in the spine; reflex sympathetic dystrophy, cervicalgia,glossodynia, carotidynia; cricoidynia; otalgia due to middle ear lesion;gastric pain; sciatica; maxillary neuralgia; laryngeal pain, myalgia ofneck muscles; trigeminal neuralgia (sometimes also termed ticdouloureux); temporomandibular joint disorder; atypical facial pain;ciliary neuralgia; paratrigeminal neuralgia (also referred to asRaeder's syndrome); musculoskeletal neck pain; petrosal neuralgia;Eagle's syndrome; idiopathic intracranial hypertension; orofacial pain;myofascial pain syndrome involving the head, neck, and shoulder;paratrigeminal paralysis; sphenopalatine ganglion neuralgia (alsoreferred to as lower-half headache, lower facial neuralgia syndrome,Sluder's neuralgia, and Sluder's syndrome); carotidynia; Vidianneuralgia; and causalgia; or any combination thereof.

C. Detection and Localization of Other Neurological Disorders

The hardware and methods described previously for detection andlocalization of epileptic activity are generally similar to those usedfor detection and localization of other neurological disorders. Forspecific movement disorders, it may be appropriate to incorporate meansfor tremor detection, which can use various types of algorithms todetect an EEG signature or other signature pertaining to the movementdisorder. For other types of neurological disorders, there is evidencethat certain electroencephalographic patterns may be evident. Empiricaldatabases can be assembled for persons suffering from saidmanifestations and the data can be used comparatively to determinewhether the patient's electroencephalogram matches any of theneurological disorder manifestations in the database. If a match isfound, an appropriate therapy can be provided to alleviate theneurological disorder. Stimulation at particular areas may be used tohelp localize and diagnose specific types of neurological disorderoriginating from specific locations by blocking pain from certain areas.

The methods of the present invention can be used to detect and localizea variety of neurological disorders, including but not limited to,neurologic diseases such as Parkinson's disease, Huntington's disease,Parkinsonism, rigidity, hemiballism, choreoathetosis, akinesia,bradykinesia, hyperkinesia, other movement disorder such as dystonia,cerebropalsy, essential tremor, and hemifacial spasms, epilepsy, orgeneralized or partial seizure disorder, Alzheimer's disease, and Pick'sdisease; psychiatric diseases, such as depression, bipolar disorder,anxiety, phobia, schizophrenia, multiple personality disorder;psychiatric disorders, such as substance abuse, attention deficithyperactivity disorder, impaired control of aggression, or impairedcontrol of sexual behavior; other neurological conditions, such as thoserelated to headaches; and concussions, post-concussive syndrome, stress,migraines, chronic headaches; and cerebrovascular diseases, such asatherosclerosis, cerebral aneurysm, stroke, cerebral hemorrhage; or anycombination thereof

3.2 Treatment and Prevention of Neurological Disorders

The bioelectric neuro device of the present invention may be used totreat and/or prevent neurological disorders. This involves theapplication of stimulation, alone or in combination with a sensoryinput, to a patient to elicit a response as a treatment. The sensoryinput may include physical manifestations, such as vibration, otherelectrical signals not directed to brain tissue (for example,somatosensory stimulation resulting in a scalp twitch or sensation inthe scalp or other part of the body), light flashes, sound pulses, etc.Other types of stimulation, e.g., via drug delivery, may also beprovided on demand from the detection sub-system.

The stimulation parameter generation algorithm residing in thestimulation controller 115 b determines to which electrodes thatelectrical stimulation shall be provided in order to reach the source,if stimulation is necessary. The stimulation parameter generationalgorithm instructs the electrode arbiter 111 to effectuate this task.

A. Treatment and Prevention of Epilepsy

A pilot study by the inventors showed that the use of electricalstimulation in the control of seizure activity of the brain is possible.This idea can easily be modified to create an internalized seizurecessation apparatus. Alternatively, both external and internalcomponents can be used.

The bioelectric neuro device of the present invention, e.g., a seizurefibrillator is used for the treatment and/or prevention of epilepsy. Inits most basic variation, the seizure fibrillator providesneurostimulation in a first mode, non-responsive (i.e., programmed)stimulation, which modulates neural activity, providing neuraldesynchronization in the brain resulting in a reduction of neurologicaldisorder events. The non-responsive stimulation and the responsivestimulation may be delivered from the same electrode, but they also maybe delivered from separate electrodes connected to the same seizurefibrillator. The location of the electrode(s) for stimulation ispreferably such that stimulation targets the focus of the neurologicaldisorder. However, this need not be the case.

Non-responsive stimulation typically is made up of low intensity, shortduration pulses delivered at a rate in the range of from about 10 Hz toabout 250 Hz. The pulses may be square pulses, or may have othermorphologies, such as exponential, sinusoidal, triangular, andtrapezoidal. The pulses may be voltage controlled, or preferably,current controlled. Generally, the pulses will be biphasic to achievecharge balance, but waveforms having a net DC component may also haveutility if used in conjunction with appropriate electrodes. To reducethe likelihood of the stimulation promoting epileptogenesis, highfrequency stimulation having a primary frequency in the range of fromabout 10 Hz to about 250 Hz (or pulse-to-pulse intervals of about 100milliseconds to about 4 milliseconds) may be used for a duration ofabout 15 sec. to about 30 min. or longer, if necessary, delivered fromthe same electrode as the responsive stimulation, or from a differentelectrode(s). The stimulation may be delivered on a scheduled basis, onan as needed basis, or per the patient's mandates.

The electrode 120 of the bioelectric neuro device is preferablycontrollable to produce output stimulating signals that can be varied involtage, frequency, pulse width, current, and intensity. Further, theelectrode 120 is preferably controllable such that the controller mayproduce both positive and negative current flow from the electrode, stopcurrent flow from the electrode, or change the direction of current flowfrom the electrode. The electrode 120 preferably has the capacity forvariable output, such as complex exponential waveforms, and linearoutput. While it is anticipated that a signal generator will typicallybe used to control the electrode 120, it should be understood that anydevice or combination of devices may be used to allow the operator toadjust the electrode as described herein.

It is recommended that the application of stimulus from the electrode120 and adjustments of the electrode parameters as described herein areperformed, preferably, under the supervision and guidance of aphysician. However, the operator may be a technician or the patient, whocould activate the electrode(s) 120 to stimulate the desired region.While it may be possible to configure the electrode(s) 120 and itscontroller such that the patient could alter the parameters of theelectrode(s) stimulus without supervision by a physician, this would notbe recommended, as the patient may not have sufficient knowledge toavoid dangers associated with misapplication of the methods disclosedherein.

In one embodiment, the electrode(s) 120 are connected to a power source(such as a battery or pulse generator) which provides the energy sourcefor the electrical stimulation. The electrode(s) 120 may be mono-polar,or multi-polar. However, the use of a multi-polar electrode ispreferred. Unipolar stimulation typically utilizes a pole and areference electrode, and requires relatively high amounts of current.Bipolar stimulation utilizes adjacent poles with current flowing fromthe negative pole (cathode) to the positive pole (anode), and causesdepolarization of nervous tissue at current levels lower than withunipolar stimulation. Whereas, multi-polar stimulation can have multipleanodes and cathodes, where one electrode could actually be an anoderelative to another electrode and a cathode relative to a more positiveelectrode. Very complex electric fields can be established within thebiological tissue with multi-polar electrode configurations, which mayhave benefits in desynchronizing epileptiform activity.

In one embodiment, the electrode 120 is controlled to produce anelectronic current for the application of stimulation. Preferably, thecurrent will comprise relatively high frequency pulses, and may possessa low frequency amplitude or frequency modulation. The exact parametersfor the electrical stimulation of the electrodes are likely to vary bypatient; however, based upon data known for stimulations performed onthe brain, parameters suitable for use herein are: a frequency in therange of from about 0.1 Hz to about 2500 Hz, preferably in the range offrom about 10 Hz to about 250 Hz, and a pulse width in the range of fromabout 10 microseconds to about 10 seconds, preferably in the range offrom about 50 microseconds to about 250 microseconds, a voltageamplitude in the range of from about 500 mv to about 2K volts,preferably in the range of from about 30 volts to about 100 volts, and acurrent amplitude in the range of from about 0.01 mA to about 1 amp (A),preferably in the range of from about 5.0 mA to about 50 mA. Shorterpulse widths are preferred for safety considerations. In anotherembodiment, high frequency bursts of current are produced on top of anunderlying low frequency continuous stimulus. Preferably, the electrodeis associated with a programmable controller, which may be utilized toproduce continuous, scheduled, or episodic, responsive stimulation. Inanother embodiment, the programmable controller is utilized to graduallyincrease stimulation to desired maximum levels. Alternatively, aprogrammable controller is utilized to immediately produce stimulationat the desired maximum level or to perform any number of intermediatesteps to reach the maximum level.

In one embodiment of the present invention, bioelectric neuro device 100is utilized for prevention of neurological events. This method involvesthe detection and analysis of brain's electrical activity to detectepileptiform activity or to detect such impending activity. If theepileptiform activity is present or is impending, responsive stimulationmay be initiated. The results of the epileptiform activity analysis mayalso be used to modify the parameters of the non-responsive stimulationto improve the suppression of seizures or other undesirable neurologicalevents. The responsive stimulation is initiated when an analysis of theEEG, or other signals, shows an impending or existent neurologicalevent, such as epileptiform activity. When the seizure onset is detectedand electrical stimulation is applied, the seizure is pre-empted. If allseizures are pre-empted, by definition, epilepsy is prevented.

In another embodiment, stimulation is applied at intermittent or presetperiods to prevent epilepsy. Electrical stimulation may be applied on anas needed basis by the epilepsy sufferer to prevent epileptic activity.If the epilepsy sufferer feels an aura, he or she may want to turn theelectrical stimulation on to pre-empt the seizure. The VNS system allowsthe patient to manually turn the stimulation on as needed. Lastingaffects have been reported due to the use of electric stimulations forseizures, implying that using stimulation for brief periods may haveprolonged benefit, such as using it prior to retiring to bed.

In another embodiment, the parameters (e.g., electrode(s) used,morphology of the stimulating signal, number of pulses or cycles of thestimulating signal, amplitude, pulse-to-pulse interval or frequency ofthe stimulating signal, duration of the stimulating signal, etc.) of theresponsive stimulation are varied. The variation of the parameters maybe based either upon a preprogrammed sequence or based upon somecharacteristic of the detected abnormal neural activity. Additionally,the parameters of the responsive stimulation are varied betweendifferent episodes of spontaneous abnormal neural activity to minimizethe tendency of the stimulation itself to predispose the brain toepileptogenesis (also known as “kindling”). Analysis of the electricalactivity of the brain can continue while stimulation is applied byanalyzing electrodes that are not being stimulated to determine whetherthe stimulation has had its desired effect.

B. Treatment and Prevention of Other Neurological Disorders

The bioelectric neuro device of the present invention, e.g., aneurostimulator, is used to for the treatment and/or prevention of otherneurological disorders. In one embodiment of the present invention, aneurostimulator provides varied stimulus intensity. The stimulation maybe activating, inhibitory, or a combination of activating andinhibitory, and the disorder is neurologic or psychiatric.

In the basic mode of operation, neurostimulator 100 is used for applyingnon-responsive stimulation, similar as for epilepsy. The stimulation maybe applied at predetermined time intervals as a preventative measure, orapplied in response to detection of a neurological disorder event. For aspecific neurological disease, such as for Parkinson's disease,stimulation is applied to disrupt the neurological activity that causesthe manifestation of the disease. In deep brain stimulation, bilateralstimulation of the thalamus or globus pallidus are typically targeted.The stimulation parameters preferable for use herein are pulses in therange of from about 100 Hz to about 200 Hz, and pulse width in the rangeof about 50 usec to about 100 usec, with a large proportion of on-to-offtimes. These stimulation techniques can all be performed non-invasively.

Both non-responsive and responsive modes can be beneficial forprevention of neurological disorders. As electrical stimulation, such aselectrocunvulsive therapy, is known to cause neurogenesis, applyingnon-responsive neurostimulation at preset intervals, or evenoccasionally, may act as a preventive maintenance mechanism for apatient's neurological system.

C. Treatment and Prevention of Pain

The pathophysiology creating the described pain is not often fullyclear. For example, in the case of migraine headaches, a number ofneurological and vascular events have been identified which take placeprior to the onset of migraine pain. Research shows that a primaryneuronal process triggers changes in dural vessels, which inducessterile inflammation that leads to activation of the trigeminal nucleusand the onset of head pain. Specifically, cortical depression suppressescortical neuronal activity in the patient, followed by activation ofmigraine centers in the brain stem, and the start of perivascularinflammation. Dilation and constriction of cranial blood vessels mayalso occur. As the main pain sensitive structures in the brain are thelarge blood vessels, the venous sinuses, and the meninges, it isbelieved that the perivascular inflammation may be the primary cause ofhead pain felt by migraine sufferers in many cases.

The large cerebral vessels, pial vessels, large venous sinuses and thesurrounding dura are innervated by a plexus of nerve fibers (which aremostly unmyelinated), that arise from the trigeminal ganglion, and theposterior fossa, that arise from the upper cervical dorsal nerve roots.This nerve fiber plexus is in the form of a sheath that wraps around thedural sinuses and blood vessels. The nerve fiber plexus contains manyinflammatory mediators. When the trigeminal ganglion is stimulated, theinflammatory mediators are released, causing sterile neurogenicinflammation of the perivascular space.

The bioelectric neuro device of the present invention can be utilized tolocalize electrical stimulation of the venous sinuses and adjacent duraor falx cerebri of the superior sagittal sinus, confluence of sinuses,occipital sinus, sigmoid sinus, transverse sinus; straight sinus;inferior sagittal sinus, or a combination thereof, using one or moreelectrodes on or under the scalp, or electrodes that are surgicallyimplanted on, in, or near the brain, or any combination thereof, fortreatment of a number of medical conditions.

In one embodiment of the present invention, the bioelectric neuro device100 is used to disrupt neurogenic inflammation by stimulating the nervefibers innervating the dural sinuses. This is accomplished by using theelectrodes 120 to deliver electrical stimuli to one or more of the duralvenous sinuses and/or the surrounding dura and falx cerebri in order tocancel signals passing through the nerve fibers, which stimulate theneurogenic inflammation. This may occur due to the stimulation ofneurons, which act to suppress the signals, or which in turn activateother neurons that act to suppress the signals, the stimulation ofneurons to directly inhibit the neurons, which may stimulate theneurogenic inflammation, or a combination of the foregoing. Suchstimulation may also act to disrupt the process by which inflammatorymediators, such as vasoactive peptide, are released from the afferentnerve fibers. The electrodes need not be in direct contact with thenerve fibers, only the stimulation current needs to contact the nervefibers.

In one embodiment, the treatment method provides pain relief bydisrupting pain signals transmitted through the nerve fibers, even withneurogenic inflammation. Once nerves are sensitized, due to neurogenicinflammation, they act as transducers and change chemical pain signalsinto electrical pain signals. The nerves then carry the generatedelectrical pain signals back to the trigeminal ganglion and then to thebrainstem and brain pain centers, resulting in the perception of pain bythe patient. The electrical stimuli applied by electrodes 120 to reachone or more of the dural venous sinuses and/or the surrounding dura andfalx cerebri can influence and modulate the transduction of the chemicalpain signals into electrical pain signals, as well as suppress orprevent the transmission of the electrical pain signals.

The methods of the present invention also pertain to the use of thebioelectric neuro device to deliver electrical stimulation viaconcentric electrodes in combination with other peripheral stimulationtechniques, such as drugs and/or sound.

While the above description of the invention has been presented in termsof a human subject (patient), it is appreciated that the invention mayalso be applicable to treating other mammals.

As noted above, the present invention is applicable to devices fordetecting, preventing, and/or treating neurological disorders, andmethods related thereto. The present invention should not be consideredlimited to the particular embodiments described above, but rather shouldbe understood to cover all aspects of the invention as fairly set out inthe appended claims. Various modifications, equivalent processes, aswell as numerous structures to which the present invention may beapplicable will be readily apparent to those skilled in the art to whichthe present invention is directed upon review of the presentspecification. The claims are intended to cover such modifications anddevices.

1. A medical device, comprising a control module, one or moreelectrodes, and a power supply, wherein, the control module comprises anelectrode arbiter, a detection sub-system, an impedance sub-system, amemory sub-system, a stimulation sub-system, a communication sub-system,and a central processing unit, and wherein each of the one or moreelectrodes comprises a multi-polar configuration.
 2. A medical deviceaccording to claim 1, wherein the detection sub-system comprises one ormore amplifiers, one or more analog-to digital converters, and a digitalsignal processor.
 3. A medical device according to claim 1, wherein theimpedance sub-system comprises one or more impedance signal generatorsand an impedance controller.
 4. A medical device according to claim 1,wherein the stimulation sub-system comprises one or more stimulationsignal generators, a stimulation controller, and a high voltage supply.5. A medical device according to claim 1, wherein the one or moreelectrodes comprise at least one outer conductive element and onecentral conductive element, wherein the at least one outer conductiveelement surrounds the central conductive element.
 6. A medical deviceaccording to claim 5, wherein the conductive elements are arranged in aconcentric geometric configuration of a ring, a square, a rectangle, anellipse, or a polygon comprising any number of sides.
 7. A medicaldevice according to claim 5, wherein the conductive elements arearranged to form a gap therebetween, and wherein the gap is equal to thewidth of the at least one outer conductive element.
 8. A medical deviceaccording to claim 5, wherein the conductive elements are arranged toform a gap therebetween, and wherein the gap is less than or equal tothe width of the at least one outer conductive element.
 9. A medicaldevice according to claim 5, wherein the one or more electrodes aresurface type or implantable type.
 10. A medical device according toclaim 5, wherein the one or more electrodes are fabricated from a metal,a non-metallic conductive material, or a combination thereof, whereinthe metal or the non-metallic conductive material is biocompatible, orcomprises a conductive biocompatible coating.
 11. A medical deviceaccording to claim 4, wherein the one or more stimulation signalgenerators provide electrical signals with waveforms, wherein thewaveforms are mono-phasic, bi-phasic, or multi-phasic.
 12. A medicaldevice according to claim 4, wherein the one or more stimulation signalgenerators provide electrical signals having a frequency in the range offrom about 0.1 Hz to about 2500 Hz, a pulse width in the range of fromabout 10

sec to about 10 sec, and a duration of from about 15 sec to about 30min.
 13. A medical device according to claim 4, wherein the one or morestimulation signal generators provide voltage in the range of from about500 mV to about 2 kV, or current in the range of from about 0.01 mA toabout 1000 mA.
 14. A medical device according to claim 1, wherein thedevice is used in the detection, prevention, treatment of a neurologicaldisorder, or any combination thereof.
 15. A medical device according toclaim 14, wherein the neurological disorder is epilepsy or anotherseizure disorder, Parkinson's Disease, Huntington's disease, Alzheimer'sdisease, Pick's disease, Parkinsonism, rigidity, hemiballism,choreoathetosis, dystonia, akinesia, bradykinesia, hyperkinesia, othermovement disorder, depression, bipolar disorder, anxiety, phobia,schizophrenia, multiple personality disorder, substance abuse, attentiondeficit hyperactivity disorder, eating disorder, impaired control ofaggression, or impaired control of sexual behavior, headache, or chronicheadache, migraine, concussion, post-concussive syndrome, stress-relateddisorder, or any combination thereof.